Process for the preparation of 1,2-dihydroquinolines

Abstract

A method for preparing 1,2-dihydroquinolines that is more flexible than the Skraup reaction is provided. The method comprises treating an ortho-alkenyl aniline with a ketone in the presence of a Lewis acid. Novel intermediates and products of this method useful as steroid receptor modulators, as well as pharmaceutical compositions and methods of use thereof are also claimed.

We claim:  
     
       1. A compound having the formula:                    
       wherein 
       R 1-6  independently represent H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, F, Cl, Br, I, CN, CF 3 , CF 2 CF 3 , CO 2 R 7  (where R 7  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), CONR 7 R 8  (where R 8  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; or where, alternatively, R 7  and R 8  combine to form a four- to seven-membered ring), OR 9  (where R 9  represents C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), NR 7 R 9 , SR 9 , SOR 9 , or SO 2 R 9 ;  
       and X represents chloro, bromo, or iodo.  
     
     
       2. A compound having the formula:                    
       wherein 
       R 1-6  independently represent H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, F, Cl, Br, I, CN, CF 3 , CF 2 CF 3 , CO 2 R 7  (where R 7  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), CONR 7 R 8  (where R 8  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; or where, alternatively, R 7  and R 8  combine to form a four- to seven-membered ring), OR 9  (where R 9  represents C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), NR 7 R 9 , SR 9 , SOR 9 , or SO 2 R 9 ;  
       X represents chloro, bromo, or iodo;  
       and P represents SiR 10 R 11 R 12  (where R 10-12  independently represent C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl); COR 13  (where R 13  represents CF 3,  C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, aryl or substituted aryl); CO 2 R 14  (where R 14  represents C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl); CONR 14 R 15  (where R 15  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; or where R 14  and R 15  taken together form a five- to seven-membered ring); benzyl or substituted benzyl; or allyl or substituted allyl.  
     
     
       3. A compound having the formula:                    
       wherein 
       R 1-6  independently represent H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, F, Cl, Br, I, CN, CF 3 , CF 2 CF 3 , CO 2 R 7  (where R 7  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), CONR 7 R 8  (where R 8  represents H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; or where, alternatively, R 7  and R 8  combine to form a four- to seven-membered ring), OR 9  (where R 9  represents C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl), NR 7 R 9 , SR 9 , SOR 9 , or SO 2 R 9 ;  
       and R 16-17  independently represent H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, OR 14  (where R 14  represents C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, allyl, substituted allyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl) or Cl; or where R 16  and R 17  taken together form a five- to seven-membered, optionally substituted ring.